A number of observations have suggested that host lymphocytes, specifically cytotoxic T cells (CTL) may play a significant role in mediating allogeneic marrow graft rejection. In a murine model system, CTL were cloned from the spleens of sublethally irradiated animals which had rejected MHC disparate marrow grafts. It was found that cloned CTL were sufficient to effect rejection of T cell depleted allogeneic marrow in lethally irradiated animals. The rejection of marrow grafts by CTL was specific for the MHC gene products expressed by the marrow cells and correlated with the cytotoxic specificity of the individual clones. Since CTL can therefore reject marrow grafts, the administration of anti-CD3 monoclonal antibody in vivo has been studied as a means to enhance engraftment of T cell depleted marrow in sublethally irradiated murine hosts. In addition, cells capable of specifically suppressing precursor CTL have been studied in vitro and in vivo. In order to similarly evaluate human CTL, xenospecific human cytotoxic responses have been studied. The fine specificity of xenoantigen recognition by human T cells suggests that in transplantation of xenogeneic tissue, as in transplantation of MHC mismatched allogeneic tissue, the particular tissue antigens, and therefore tissue typing, may be a relevant consideration. The generation of human CTL has been characterized and certain essential cellular interactions in that generation have been identified.